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CD28 family of receptors on T cells in chronic HBV infection: Expression characteristics, clinical significance and correlations with PD-1 blockade.

Tang ZS, Hao YH, Zhang EJ, Xu CL, Zhou Y, Zheng X, Yang DL - Mol Med Rep (2016)

Bottom Line: The expression levels of the CD28 family receptors in the T cells of patients with CHB demonstrated distinct characteristics , for example levels of PD‑1 and CTLA‑4 on CD4 T cells and ICOS, PD‑1, and BTLA on CD8 T cells were increased in cells from patients with CHB compared with those from the healthy individuals.A significant positive correlation was demonstrated among the serum HBV DNA titers and the levels of PD‑1 on CD8+ T cells with the highest expression of PD‑1 corresponding to viral levels >106 IU/ml.A significant positive correlation was observed between the serum HBV DNA titers and the expression levels of BTLA on CD8+ T cells with the highest expression of BTLA corresponding to viral levels >106 IU/ml.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

ABSTRACT
The aim of the present study was to investigate the overall clinical expression characteristics of the cluster of differentiation (CD)28 family receptors [CD28, inducible T-cell co-stimulator, programmed cell death protein 1 (PD‑1), cytotoxic T-lymphocyte-associated protein 4 and B‑ and T-lymphocyte attenuator] on T cells in patients with chronic hepatitis B (CHB), analyze the correlations among these receptors and the clinical parameters, and to investigate the effects of PD‑1 blockade on the receptor expression profiles, T‑cell function and other biological effects. The expression characteristics of the CD28 family of receptors, the effects of PD‑1 blockade on the receptor expression profiles and the levels of interferon (IFN)‑γ were investigated in the T cells of patients with CHB. In addition, the transcription factor, T‑box 21 (T‑bet) and GATA binding protein 3 (GATA‑3) mRNA expression levels were investigated in the peripheral blood mononuclear cells (PBMCs) of patients with CHB. The expression levels of the CD28 family receptors in the T cells of patients with CHB demonstrated distinct characteristics , for example levels of PD‑1 and CTLA‑4 on CD4 T cells and ICOS, PD‑1, and BTLA on CD8 T cells were increased in cells from patients with CHB compared with those from the healthy individuals. A significant positive correlation was demonstrated among the serum HBV DNA titers and the levels of PD‑1 on CD8+ T cells with the highest expression of PD‑1 corresponding to viral levels >106 IU/ml. A significant positive correlation was observed between the serum HBV DNA titers and the expression levels of BTLA on CD8+ T cells with the highest expression of BTLA corresponding to viral levels >106 IU/ml. PD‑1 blockade altered the expression profiles of CD28 family receptors in the T cells of patients with CHB, partly enhanced T cell function and increased the ratio of T‑bet/GATA‑3 mRNA in PBMCs. Thus, CD28 family receptors are potential clinical indicators for the rapid monitoring of changes in T cell function during CHB treatment. Furthermore, PD‑1 blockade has a therapeutic potential that may be enhanced by modulating the expression of co-stimulatory and -inhibitory receptors of the CD28 family.

No MeSH data available.


Related in: MedlinePlus

Effects of PD-1 blockade on the production of T-bet and GATA-3 mRNA. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients were stimulated with HBcAg18-27 peptide for 10 days in the presence of anti-PD-L1 or isotype control. Totol mRNA was purified by TRIzol reagent, and T-bet and GATA-3 were qualified by real time PCR. (A) Expression of T-bet and GATA-3 mRNA in cells treated with anti-PD-L1 or isotype control. (B) Correlation among the gene expression fold changes of T-bet and GATA-3. (C) Ratio of T-bet: GATA-3 following anti-PD-L1 or isotype antibody treatment. (D) Correlation among the ratio of T-bet: GATA-3 and IFN-γ fold changes in CD4 T cells treated by anti-PD-L1 antibody. CHB, chronic hepatitis B; IFN-, interferon; PD-L1, PD-Ligand 1.
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f5-mmr-14-02-1107: Effects of PD-1 blockade on the production of T-bet and GATA-3 mRNA. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients were stimulated with HBcAg18-27 peptide for 10 days in the presence of anti-PD-L1 or isotype control. Totol mRNA was purified by TRIzol reagent, and T-bet and GATA-3 were qualified by real time PCR. (A) Expression of T-bet and GATA-3 mRNA in cells treated with anti-PD-L1 or isotype control. (B) Correlation among the gene expression fold changes of T-bet and GATA-3. (C) Ratio of T-bet: GATA-3 following anti-PD-L1 or isotype antibody treatment. (D) Correlation among the ratio of T-bet: GATA-3 and IFN-γ fold changes in CD4 T cells treated by anti-PD-L1 antibody. CHB, chronic hepatitis B; IFN-, interferon; PD-L1, PD-Ligand 1.

Mentions: The results of the current study demonstrated that the total gene expression levels of T-bet and GATA-3 in PBMCs were increased following anti-PD-L1 exposure (T-bet Control vs. Anti-PD-L1; P=0.0006; GATA-3 Contol vs. Anti-PD-L1; P=0.0172; Fig. 5A). A positive correlation was demonstrated among the fold-changes of T-bet and GATA-3 (P=0.0435; Fig. 5B) and following anti-PD-L1 exposure, the rate of T-bet/GATA-3 was increased (P=0.0209; Fig. 5C). In addition, a positive correlation was identified between the IFN-γ fold-change and the rate of T-bet/GATA-3 (P=0.0259; Fig. 5D).


CD28 family of receptors on T cells in chronic HBV infection: Expression characteristics, clinical significance and correlations with PD-1 blockade.

Tang ZS, Hao YH, Zhang EJ, Xu CL, Zhou Y, Zheng X, Yang DL - Mol Med Rep (2016)

Effects of PD-1 blockade on the production of T-bet and GATA-3 mRNA. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients were stimulated with HBcAg18-27 peptide for 10 days in the presence of anti-PD-L1 or isotype control. Totol mRNA was purified by TRIzol reagent, and T-bet and GATA-3 were qualified by real time PCR. (A) Expression of T-bet and GATA-3 mRNA in cells treated with anti-PD-L1 or isotype control. (B) Correlation among the gene expression fold changes of T-bet and GATA-3. (C) Ratio of T-bet: GATA-3 following anti-PD-L1 or isotype antibody treatment. (D) Correlation among the ratio of T-bet: GATA-3 and IFN-γ fold changes in CD4 T cells treated by anti-PD-L1 antibody. CHB, chronic hepatitis B; IFN-, interferon; PD-L1, PD-Ligand 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940091&req=5

f5-mmr-14-02-1107: Effects of PD-1 blockade on the production of T-bet and GATA-3 mRNA. Peripheral blood mononuclear cells derived from HLA-A2+ CHB patients were stimulated with HBcAg18-27 peptide for 10 days in the presence of anti-PD-L1 or isotype control. Totol mRNA was purified by TRIzol reagent, and T-bet and GATA-3 were qualified by real time PCR. (A) Expression of T-bet and GATA-3 mRNA in cells treated with anti-PD-L1 or isotype control. (B) Correlation among the gene expression fold changes of T-bet and GATA-3. (C) Ratio of T-bet: GATA-3 following anti-PD-L1 or isotype antibody treatment. (D) Correlation among the ratio of T-bet: GATA-3 and IFN-γ fold changes in CD4 T cells treated by anti-PD-L1 antibody. CHB, chronic hepatitis B; IFN-, interferon; PD-L1, PD-Ligand 1.
Mentions: The results of the current study demonstrated that the total gene expression levels of T-bet and GATA-3 in PBMCs were increased following anti-PD-L1 exposure (T-bet Control vs. Anti-PD-L1; P=0.0006; GATA-3 Contol vs. Anti-PD-L1; P=0.0172; Fig. 5A). A positive correlation was demonstrated among the fold-changes of T-bet and GATA-3 (P=0.0435; Fig. 5B) and following anti-PD-L1 exposure, the rate of T-bet/GATA-3 was increased (P=0.0209; Fig. 5C). In addition, a positive correlation was identified between the IFN-γ fold-change and the rate of T-bet/GATA-3 (P=0.0259; Fig. 5D).

Bottom Line: The expression levels of the CD28 family receptors in the T cells of patients with CHB demonstrated distinct characteristics , for example levels of PD‑1 and CTLA‑4 on CD4 T cells and ICOS, PD‑1, and BTLA on CD8 T cells were increased in cells from patients with CHB compared with those from the healthy individuals.A significant positive correlation was demonstrated among the serum HBV DNA titers and the levels of PD‑1 on CD8+ T cells with the highest expression of PD‑1 corresponding to viral levels >106 IU/ml.A significant positive correlation was observed between the serum HBV DNA titers and the expression levels of BTLA on CD8+ T cells with the highest expression of BTLA corresponding to viral levels >106 IU/ml.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

ABSTRACT
The aim of the present study was to investigate the overall clinical expression characteristics of the cluster of differentiation (CD)28 family receptors [CD28, inducible T-cell co-stimulator, programmed cell death protein 1 (PD‑1), cytotoxic T-lymphocyte-associated protein 4 and B‑ and T-lymphocyte attenuator] on T cells in patients with chronic hepatitis B (CHB), analyze the correlations among these receptors and the clinical parameters, and to investigate the effects of PD‑1 blockade on the receptor expression profiles, T‑cell function and other biological effects. The expression characteristics of the CD28 family of receptors, the effects of PD‑1 blockade on the receptor expression profiles and the levels of interferon (IFN)‑γ were investigated in the T cells of patients with CHB. In addition, the transcription factor, T‑box 21 (T‑bet) and GATA binding protein 3 (GATA‑3) mRNA expression levels were investigated in the peripheral blood mononuclear cells (PBMCs) of patients with CHB. The expression levels of the CD28 family receptors in the T cells of patients with CHB demonstrated distinct characteristics , for example levels of PD‑1 and CTLA‑4 on CD4 T cells and ICOS, PD‑1, and BTLA on CD8 T cells were increased in cells from patients with CHB compared with those from the healthy individuals. A significant positive correlation was demonstrated among the serum HBV DNA titers and the levels of PD‑1 on CD8+ T cells with the highest expression of PD‑1 corresponding to viral levels >106 IU/ml. A significant positive correlation was observed between the serum HBV DNA titers and the expression levels of BTLA on CD8+ T cells with the highest expression of BTLA corresponding to viral levels >106 IU/ml. PD‑1 blockade altered the expression profiles of CD28 family receptors in the T cells of patients with CHB, partly enhanced T cell function and increased the ratio of T‑bet/GATA‑3 mRNA in PBMCs. Thus, CD28 family receptors are potential clinical indicators for the rapid monitoring of changes in T cell function during CHB treatment. Furthermore, PD‑1 blockade has a therapeutic potential that may be enhanced by modulating the expression of co-stimulatory and -inhibitory receptors of the CD28 family.

No MeSH data available.


Related in: MedlinePlus